Session Type: Poster Session (Tuesday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Dermatomyositis (DM) is a progressive, systemic autoimmune disease-causing inflammatory changes in the skin and skeletal muscles. DM is associated with carcinomas of the ovary, breast, lung and GI tract in a significant number of patients.
Methods: We employed the STARGEO platform to search the Gene Expression Omnibus and conduct meta-analysis on muscle biopsy (71 DM vs 22 healthy). We then analyzed the signature using Ingenuity Pathway Analysis, restricting genes that showed statistical significance (p< 0.05) and an absolute experimental log ratio greater than 0.1. We focused our analysis on tumorigenic gene expression.
Results: Our data demonstrate activation of several tumorigenesis associated genes: a) Immunoglobulin lambda constant 1 (IGLC1; p-value 4.48e-10, log ratio 2.62) is part of the innate immune response but is also upregulated in chronic myeloid leukemia, T-cell lymphoma, and T-cell non-Hodgkin disease, b) IFI44 (p-value 0.0377, log ratio 2.40) upregulated in both cutaneous and muscle samples of DM, is also upregulated in T-cell non-Hodgkin disease, and in peripheral and cutaneous T-cell lymphomas, c) Periostin (POSTN; p-value 0.0359, log ratio 2.15) is a secreted extracellular matrix protein part of the FAS1 domain, binds to integrins to support adhesion and migration of epithelial cells, and plays a role in cancer stem cell maintenance and metastasis and d) the MYC (p-value 0.0414, log ratio 1.28) proto-oncogene. Further tumorigenesis pathways identified in our dataset include CD44 (p-value 0.0343, log ratio 0.886), NPM1 (p-value 0.0295, log ratio 0.462), and IDO1 (p-value 0.0109, log ratio 0.543). CD44 is a cell surface adhesion receptor that is overexpressed in cancer cells and regulates metastasis and is considered a stem cell marker in ovarian cancer and an indicator of poor prognosis. Overexpression of NPM1 is a marker for progression in solid tumors such as hepatocellular and ovarian carcinomas and in some breast cancers. Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan catabolic enzyme that is also implicated in tumorigenesis via promotion of immune tolerance to tumor antigens.
Conclusion: Our results demonstrate novel tumorigenesis related pathways that are upregulated in Dermatomyositis that have largely not been studied previously in this disease. Additional studies need to be carried out to determine if this tumorigenic gene overexpression can serve as a predictive biomarker of malignancy risk in DM. Moreover, since some of the genes (e.g. IDO) are being studied as target for anticancer therapy, this should be explored in patients with DM associated malignancy also.
To cite this abstract in AMA style:Aljabban J, Syed S, Syed S, Hoffman K, Hasan L, Adapa N, Allarakhia Z, Hadley D, Aljabban M, Jarjour W. Tumorigenesis Related Gene Identification in Dermatomyositis Using Meta-Analysis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/tumorigenesis-related-gene-identification-in-dermatomyositis-using-meta-analysis/. Accessed November 26, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tumorigenesis-related-gene-identification-in-dermatomyositis-using-meta-analysis/